Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation
in this study:
1. Males or females, age 18 to 75 years of age.
2. ECOG performance status score of 0, 1 or 2.
3. Life expectancy of at least 9 months. 4. Measurable disease according to the IMWG criteria defined as. 1. Serum monoclonal paraprotein (M-protein) ≥ 10 g/L (if IgG) or ≥5g/L (if IgA, D, E
or M)
2. Urine M-protein ≥ 200 mg/24 h. 3. Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/L and an
abnormal serum free light chain ratio (< 0.26 or > 1 .65) if no M-protein
detected in serum or urine. 5. Newly Diagnosed Symptomatic Multiple Myeloma by IMWG criteria. 6. The following laboratory results must be met within 10 days of first study drug
administration:
1. ANC ≥ 1.0 x 109/L. 2. Hemoglobin ≥ 80 g/L (transfusions permitted)
3. Platelets ≥ 70 x 109/L (or ≥50 x 109/L if ≥50% plasmacytosis in bone marrow.
4. Calculated CrCl ≥ 30 mL/min. 5. AST and ALT ≤ 3.0 x ULN. 6. Total bilirubin ≤ 2 x ULN unless known to have Gilbert's disease. 7. Corrected serum calcium ≤ 3.5 mmol/L. 7. Have signed the informed consent documents indicating that the subject understands the
purpose of and procedures required for the study and is willing to participate and
adhere to the study protocol.
8. Females with child-bearing potential (FCBP) must agree to use 2 reliable forms of
contraception* simultaneously or practice complete abstinence from heterosexual
contact for at least 28 days before starting study drug, while participating in the
study (including during dose interruptions), and for at least 150 days after study
treatment discontinuation.
9. Females must agree to abstain from breastfeeding during study participation and 150
days after study drug discontinuation.
10. Males must agree to use a latex condom during any sexual contact with FCBP while
participating in the study and for 150 days following discontinuation from this study,
even if he has undergone a successful vasectomy.
11. Males must also agree to refrain from donating semen or sperm during the treatment
phase and for 150 days after discontinuation from this study treatment.
12. All subjects must agree to refrain from donating blood while on study therapy and for
28 days after discontinuation from this study treatment.
Females of childbearing potential (FCBP): a female of childbearing potential is a sexually
mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has
not been naturally postmenopausal for at least 24 consecutive months).
* The two methods of birth control used may be selected from the following categories, but
the two methods cannot be selected from any one category: barrier method: i.e., condom
(male or female) or diaphragm with spermicide; hormonal: i.e., contraceptive pill, patch;
intrauterine device (IUD); vasectomy; or tubal ligation.
Exclusion Criteria:
Subjects who meet any of the following exclusion criteria are not eligible for enrollment:
1. Prior exposure to Isatuximab (or other anti-CD38 monoclonal antibody)
2. Prior treatment for Multiple Myeloma (MM) with the exception of corticosteroids not
exceeding a total dose specified below:
3. Subjects who have received steroids within 2 weeks prior to starting study treatment
or who have not recovered from side effects of such therapy. Concomitant therapy
medications that include corticosteroids are allowed if subject receive ≤10 mg of
prednisone per day, or equivalent, as indicated for other medical conditions, or up to
100 mg of hydrocortisone as pre-medication for administration of certain medications
or blood products prior to enrolment in this study.
4. Prior history of malignancies, other than MM, unless the subject has been free of the
disease for 3 years or longer. Exceptions include the following:
1. Basal or squamous cell carcinoma of the skin. 2. Carcinoma in situ of the cervix or breast. 3. Adenocarcinoma of the prostate (TNM stage of T1 a or T1 b)
5. Other concurrent severe and/or uncontrolled medical conditions (i.e. uncontrolled
diabetes, active or uncontrolled infection, acute diffuse pulmonary disease,
pericardial disease, uncontrolled thyroid dysfunction or uncontrolled severe arterial
hypertension) including abnormal laboratory values, that could cause unacceptable
safety risks or compromise compliance with the protocol. 6. History of or current uncontrolled cardiovascular disease including:
1. Unstable angina, myocardial infarction, or known congestive heart failure Class
III/IV (Appendix 5) within the preceding 12 months. 2. Transient ischemic attack within the preceding 3 months, pulmonary embolism
within the preceding 2 months.
3. Any of the following: sustained ventricular tachycardia, ventricular
fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart
block or third-degree heart block; known presence of dilated, hypertrophic, or
restrictive cardiomyopathy.
4. QTc prolongation as confirmed by ECG assessment at screening (QTc >470
milliseconds).
5. Poorly controlled severe arterial hypertension.
7. Women who are pregnant, breastfeeding or planning to become pregnant while enrolled in
this study, or within 90 days after the last dose of study medications. Male subject
who plans to father a child while enrolled in this study, within 90 days after the
last dose of study medications.
8. Known HIV positivity or active infectious hepatitis B or C. 9. Known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies
or human proteins, or their excipients (refer to the Isatuximab IB), or known
sensitivity to mammalian-derived products, if not amenable to premedication with
steroids, or H2 blockers that would prohibit further treatment with these agents.
10. Known CNS involvement, plasma cell leukemia or amyloidosis.
11. Subjects who are receiving any other investigational agent Any other condition that,
in the Investigator's opinion, would contraindicate the patient's participation in the
clinical study due to safety concerns or compliance with clinical study procedures.
